Diuretics (versus unexposed) - Medication and Pregnancy KB

Diuretics (versus unexposed)

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Fisher b - Diuretics (Controls unexposed, disease free), 2018	USA 1997 - 2011	Non-malformed singleton live births randomly selected from birth certificates or hospital discharge records in 10 study sites participating in the National Birth Defects Prevention Study (NBDPS).	Mother with hypertension (chronic or pregnancy-related) that reported use of Diuretics at any time during the month before pregnancy until delivery.	unexposed, disease free Normotensive mothers who did not report taking an antihypertensive medication during pregnancy.	15 / 10050	Most (83.0%) mothers who began using an antihypertensive medication before or during the first trimester continued use in the second trimester or later (data not shown).
Fisher b - Diuretics (Controls unexposed, sick), 2018	USA 1997 - 2011	Non-malformed singleton live births randomly selected from birth certificates or hospital discharge records in 10 study sites participating in the National Birth Defects Prevention Study (NBDPS).	Mother with hypertension (chronic or pregnancy-related) that reported use of Diuretic at any time during the month before pregnancy until delivery.	unexposed, sick Mother with untreated hypertension (chronic or pregnancy-related).	15 / 839	Most (83.0%) mothers who began using an antihypertensive medication before or during the first trimester continued use in the second trimester or later (data not shown).
Leather - Bendrofluazide, 1968	United Kingdom Not specified.	Patients that were referred from the antenatal clinics and from obstetric wards, diagnosed with early (before 20 weeks of gestation) or late (normontensive before 20 weeks) hypertension.	Pregnant patients with early hypertension (before 20 gestational weeks) randomly allocated to treatment group, i.e bendrofluazide 5-10 mg daily with potassium supplements and methyldopa 0-5-2g daily in divided doses.	unexposed, sick Pregnant patients with early hypertension (before 20 gestational weeks) randomly allocated to control group.	23 / 24	Data related to chronic hypertension were reported here.
Mabie - Hydrochlorothiazide, 1986	USA 1980 - 1984	Pregnant women with chronic hypertension (>= 140/90 mmHg before pregnancy or at less than 20 week's gestation) who delivered at this hospital during the study period.	Pregnant women with chronic hypertension treated with Hydrochlorothiazide only.	unexposed, sick Pregnant women with chronic hypertension without treatment.	10 / 82	Data on Hydrochlorothiazide only reported rather than co-administration Methyldopa and hydrochlorothiazide.
Olesen_Denmark - Diuretics, 2001	Denmark 1991 - 1998	Women who gave birth (to a singleton) in the county during the study period.	Pregnant women who purchased prescription diuretics (1) any time during their pregnancy and (2) during their third trimester.	unexposed (general population or NOS) Pregnant women who did not purchase prescription diuretics during their pregnancy.	315 / 46998
Olesen_Scotland - Diuretics, 2001	Scotland 1993 - 1995	Women who gave birth (to a singleton) in the county during the study period.	Pregnant women who purchased prescription diuretics (1) any time during their pregnancy and (2) during their third trimester.	unexposed (general population or NOS) Pregnant women who did not purchase prescription diuretics during their pregnancy.	73 / 35798
Sibai - Diuretics, 1984	USA Not specified.	Pregnant women with a documented history of mild-to-moderate long-term hypertension who were receiving diuretics prior to pregnancy.	Pregnant women receiving diuretics in their first trimester and then randomly assigned to the group allowed to continue their diuretic medication throughout the course of pregnancy.	unexposed, sick Pregnant women receiving diuretics in their first trimester and then randomly assigned to the group that discontinued their diuretic medication immediately.	10 / 10	All women received diuretics at the entry into the study (1st trimester) and were then randomly to continue or discontinue => outcomes potentially impacted by exposure during first trimester (superimposed pre-eclampsia, SGA, preterm) not reported here.
Su - Diuretics (Controls unexposed, disease free), 2013	Taiwan Jan 2005 - Dec 2005	All pregnant women in Taiwan, resulting in singletons.	Pregnant women with chronic hypertension (HTN) that have received a prescription of a diuretic drug for a period of at least 30 days during any time of their pregnancy.	unexposed, disease free Pregnant women with no diagnosis of chronic hypertension (HTN), randomly selected from the same cohort.	371 / 8181	Women who used more than one type of anti-hypertensive drugs were excluded (n = 722).
Su - Diuretics (Controls unexposed, sick), 2013	Taiwan Jan 2005 - Dec 2005	All pregnant women in Taiwan, resulting in singletons.	Pregnant women with chronic hypertension (HTN) that have received a prescription of diuretics for a period of at least 30 days during any time of their pregnancy.	unexposed, sick Pregnant women with chronic hypertension (HTN) who had not used any anti-hypertensive drugs.	371 / 1006	Women who used more than one type of anti-hypertensive drugs were excluded (n = 722).
Vaclavik - Diuretics, 2024	The Czech Republic 2012 - 2022	All births and abortions in the period 2012 - 2022 in the Czech Republic.	Births whose mothers were prescribed Diuretics during pregnancy (for pre-existing hypertension or pregnancy-induced hypertension).	unexposed, disease free Births whose mothers had no hypertension.	-9 / -9
Van der Zande - Diuretics, 2024	Worldwide 2007 - 2018	Pregnant patients with structural heart disease, included in the Registry from 2007 up to 2018.	Pregnant women who used diuretics at any point during pregnancy, excluding use only during delivery or only prior to pregnancy.	unexposed, sick Pregnant women who did not use diuretics during pregnancy.	382 / 5357	Structural heart disease: including congenital and valvular heartdisease, prosthetic heart valves, cardiomyopathy, ischaemic heart disease, aortopathy and pulmonary arterial hypertension. Furosemide was by far the most frequently used diuretic (86%).

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Caton - Diuretics, 2009	USA 1997 - 2003	Cases of cardiovascular malformations in live births, fetal deaths occurring after 20 weeks, and elective pregnancy terminations.	Live births without birth defects randomly selected from birth certificates or hospital discharge listings in the same geographic areas as the cases.	5021 / 4796	Overlapping: Fisher 2017 included data published by Caton 2009 based on a longer period study (1997-2011 versus 1977-2003), more cases and 2 control groups. Fisher 2017 was used rather than Caton 2009 (except for Ebstein anomaly and aorta coarctation).
Czeizel - Furosemide, 1999	Hungary 1980 - 1996	Newborn infants (including infant deaths and usual stillborn fetuses) with congenital abnormalities.	Newborn infants (including infant deaths and usual stillborn fetuses) without congenital abnormalities, matched according to gender, birth week and district of parents’ residence.	22865 / 38151	This register is used to study several diuretics. To avoid redundancy of case and controls, only 1 of these substances was used in the class meta-analysis: this one with more exposed cases in T1 or higher OR if equal nbs => NTD not reported here.
Fisher - Diuretics (Controls unexposed, disease free), 2017	USA 1997 - 2011	Cases of cardiovascular malformations in live births, fetal deaths occurring after 20 weeks, and elective pregnancy terminations. (According to Caton 2009)	Nonmalformed live births randomly selected from birth certificates or hospital discharge records in each study site.	10625 / 11137	Overlapping: Fisher 2017 included data published by Caton 2009 based on a longer period study (1997-2011 versus 1977-2003), more cases and 2 control groups. Fisher 2017 was used rather than Caton 2009 (except for Ebstein anomaly and aorta coarctation).
Fisher - Diuretics (Controls unexposed, sick), 2017	USA 1997 - 2011	Cases of cardiovascular malformations in live births, fetal deaths occurring after 20 weeks, and elective pregnancy terminations. (According to Caton 2009)	Nonmalformed live births randomly selected from birth certificates or hospital discharge records in each study site.	10625 / 11137	Overlapping: Fisher 2017 included data published by Caton 2009 based on a longer period study (1997-2011 versus 1977-2003), more cases and 2 control groups. Fisher 2017 was used rather than Caton 2009 (except for Ebstein anomaly and aorta coarctation).
Fisher a - Diuretics, 2018	USA 1997 - 2011	All cases (liveborn, stillborn after 20 weeks gestation, or induced abortions) with an eligible defect within the study time period and geographic areas.	Live births not affected by a birth defect randomly selected from birth certificates or hospital discharge records to represent the base population from which cases were selected in each study site.	17038 / 11477	Only OR provided by authors were reported (raw data not reported) because of discrepancies between crude OR provided by authors and raw data. Outcomes without OR provided by authors not reported here.
Kramer - Diuretics, 1987	USA 1970 - 1979	Infants diagnosed with neuroblastoma, histologically confirmed.	Randomly selected sibling without neuroblastoma within the cases family.	86 / -9	Authors provided 90% confidence intervals and 2 control groups: 1 selected by telephone random digit dialing and 1 among sibling of cases's family => Sibling control preferred because more potential confounders (genetic, environ.) took into consideration.
McCredie - Diuretics, 1994	Australia 1985 - 1989	All children aged 0 to 14 years, who were newly diagnosed with a primary malignant tumour of the brain (ICD-9 191) or cranial nerves (ICD-9 192.0) reported to the NSW Central Cancer Registry.	Children matched by age and sex randomly selected in a random sample of children of women aged 20 to 55 years and living in the designated area.	82 / 164
Medveczky - Hydrochlorothiazide, 2004	Hungary 1980 - 1996	Newborn infants (including infant deaths and usual stillborn fetuses) with Neural tube defects with non-syndromic (i.e. isolated anencephaly, spina bifida aperta/cystica, encephalocele).	Newborn infants (including infant deaths and usual stillborn fetuses) without congenital abnormalities.	1202 / 38151	This register is used to study several diuretics. To avoid redundancy of case and controls, only 1 of these substances was used in the class meta-analysis: this one with more exposed cases in T1 or higher OR if equal nbs (i.e. Hydrochlorothiazide).
Nakhai-Pour - Diuretics, 2010	Canada 1998 - 2003	Mothers who gave birth to a baby with a major congenital malformation (1st study). Newborns small for gestational age (a birth weight less than the 10th percentile for that gestational age and gender according to the Canadian gender-specific references) (2nd study).	Mothers who gave birth to babies without any major or minor congenital malformation diagnosed during the same time period (1st study). Newborns not small for gestational age (2nd study).	4155 / 54878	Sum of Diuretics thiazide and K sparing diuretics (possible because monotherapy). Major congenital malformations: number of cases: 4,155; number of controls: 54,878.Small-for-gestational-age: number of cases: 7,445; number of controls: 48,889.
Orimoloye - Diuretics, 2024	Taiwan 2004 - 2015	Infants with cancer (all types) diagnosed before age 13.	Infants without cancer (all types) at the age 13.	2780 / 2291512
Schwartzbaum - Diuretics, 1992	USA 1979 - 1986	Children under age 9 years, newly diagnosed with neuroblastoma.	Children under age 9 years, newly diagnosed with acute lymphocytic leukemia, Wilms' tumor, acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, rhabdomyosarcoma, Hodgkin's disease, Ewing's sarcoma, soft tissue sarcoma, and osteosarcoma.	101 / 690
Sorensen - Diuretics, 2003	Denmark 1959 - 1961	Schizophrenia in the offspring.	Cohort comparison subjects (NOS).	84 / 7782	'The definition used here most likely included both cases of chronic hypertension and cases of gestational hypertension.'
Van Gelder - Diuretics, 2015	USA and Canada 1998 - 2010	Liveborn or stillborn infants with one of the selected birth defects without chromosomal abnormalities or associated syndromes.	Liveborn infants without birth defects randomly selected from state-wide birth records or from study hospitals covering the geographic catchment areas where the cases were identified.	5568 / 7253	Any use of antiadrenergic agents, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, or direct vasodilators at any time from the month before pregnancy to the end of pregnancy.
Van Zutphen - Diuretics, 2014	USA 1997 - 2009	All cases (liveborn, stillborn after 20 weeks gestation, or induced abortions) with severe hypospadias (ie, subcoronal or penile, scrotal, or perineal meatal opening) diagnosed at the time of physical examination, surgery, or autopsy.	Male live births without birth defects randomly selected from birth certificates or hospital discharge listings in the same population as the case neonates.	2131 / 5129	Mothers reporting antihypertensive medications for the treatment of other indications (eg, b-blockers for migraine headaches) were excluded from the analyses. Overlapping: Caton 2008 (1997-2002) totally included in Van Zutphen 2014 (1997-2009).

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